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Plasmid-Mediated Quinolone Resistance

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  • Authors: George A. Jacoby1, Jacob Strahilevitz2, David C. Hooper3
  • Editors: Marcelo Tolmasky4, Juan Carlos Alonso5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Lahey Hospital and Medical Center, Burlington, MA 01805; 2: Hadassah-Hebrew University, Jerusalem 91120 Israel; 3: Massachusetts General Hospital, Boston, MA 02114; 4: California State University, Fullerton, CA; 5: Centro Nacional de Biotecnología, Cantoblanco, Madrid, Spain
  • Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
  • Received 12 December 2013 Accepted 16 December 2013 Published 24 October 2014
  • George A. Jacoby, george.a.jacoby@lahey.org
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  • Abstract:

    Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes and code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6′)-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.

  • Citation: Jacoby G, Strahilevitz J, Hooper D. 2014. Plasmid-Mediated Quinolone Resistance. Microbiol Spectrum 2(5):PLAS-0006-2013. doi:10.1128/microbiolspec.PLAS-0006-2013.

Key Concept Ranking

Mobile Genetic Elements
0.60119677
Transcription Start Site
0.51733184
Genetic Elements
0.4137268
DNA Topoisomerase IV
0.41368032
0.60119677

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/content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0006-2013
2014-10-24
2017-11-18

Abstract:

Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes and code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6′)-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.

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FIGURE 1

The rod-like structure of the QnrB1 dimer is shown above, with the sequence of the monomer below. The sequence is divided into four columns representing the four faces of the right-handed quadrilateral β-helix. Face names and color are shown at the top along with the naming convention for the five residues of the pentapeptide repeats. Loops A and B are indicated by one and two asterisks, respectively, with their sequences indicated below and the loops shown as black traces on the diagram. The N-terminal α-helix is colored pink. The molecular 2-fold symmetry is indicated with a black diamond. Type II turn-containing faces are shown as spheres, and type IV-containing faces as strands ( 235 ). Adapted from the ( 44 ), copyright 2011, the American Society for Biochemistry and Molecular Biology. doi:10.1128/microbiolspec.PLAS-0006-2013.f1

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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FIGURE 2

QnrB1 protection of DNA gyrase from ciprofloxacin inhibition of supercoiling. Reaction mixtures of 30 µl were analyzed by agarose gel electrophoresis. Reaction mixtures contained 0.2 µg relaxed pBR322 DNA (lanes 1 to 14), 6.7 nM gyrase (lanes 2 to 14), 2 µg/ml ciprofloxacin (lanes 3 to 14), and QnrB-His6 fusion protein at 25 µM (lane 4), 5 µM (lane 5), 2.5 µM (lane 6), 0.5 µM (lane 7), 50 nM (lane 8), 5 nM (lane 9), 0.5 nM (lane 10), 50 pM (lane 11), 5 pM (lane 12), or 0.5 pM (lane 13). Reprinted from reference 27 . doi:10.1128/microbiolspec.PLAS-0006-2013.f2

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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FIGURE 3a

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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FIGURE 3b

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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FIGURE 3c

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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FIGURE 4

Survival at increasing fluoroquinolone concentrations for J53 and J53 pMG252. A large inoculum (10 colony forming units) and appropriate dilutions were applied to Mueller-Hinton agar plates containing the indicated concentration of ciprofloxacin, and surviving colonies were counted after incubation for 72 h at 37°C. doi:10.1128/microbiolspec.PLAS-0006-2013.f4

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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Tables

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TABLE 1

Representative plasmids and transmissible PMQR genes

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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TABLE 2

Distribution of PMQR genes

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013
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TABLE 3

Effect of different quinolone resistance mechanisms on quinolone susceptibility of

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.PLAS-0006-2013

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